RNA modifications in cancer and their detection: a review
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Updated: Jan 31, 2026
Characterizing RNA Modifications in Single Neurons Using Mass Spectrometry
Published on: April 21, 2022
Bo-Yi Yu1, Hiroki Ueda1,2
1Advanced Data Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo, 153-8904, 4-6-1 Komaba Meguro-ku Tokyo, Japan.
Abstract:
Ribonucleic acid (RNA) modifications, once viewed as static structural features, are now recognized as dynamic regulators of the 'epitranscriptome' that shape RNA fate. In cancer, dysregulation of RNA-modification writers, erasers, and readers reprograms RNA metabolism and translation, promoting tumorigenesis, metastasis, therapy resistance, and immune evasion. Across messenger RNAs, ribosomal RNA (rRNAs), transfer (tRNAs), and diverse non-coding RNAs, aberrant modification patterns drive alternative splicing, generate onco-ribosomes, enforce codon-biased translation, and remodel gene-expression networks in a context-dependent manner. This review summarizes how major RNA modifications-including m6A, m5C, pseudouridine, inosine, and ac4C-and their regulators contribute to cancer biology, together with disease-associated changes in rRNA, tRNA, and regulatory non-coding RNAs. We then discuss emerging diagnostic and prognostic biomarkers, druggable nodes within the epitranscriptomic machinery, and combination strategies that integrate RNA-modification targeting with existing therapies and immunotherapy. Finally, we outline key technologies for mapping RNA modifications, comparing mass spectrometry and NGS-based chemical or antibody-enrichment approaches with the expanding capabilities of nanopore direct RNA sequencing. Recent advances in nanopore direct RNA sequencing technologies, leveraging new chemistry (e.g. RNA004) and deep-learning basecallers (e.g. Dorado), increasingly enable single-molecule, multi-modification profiling, accelerating discovery despite inherent technical challenges. Collectively, biological, clinical, and technological progress is transforming the epitranscriptome into a tractable dimension of cancer biology and a promising source of future biomarkers and RNA-targeted precision therapies.
Insights
RNA modifications are dynamic regulators in cancer, influencing RNA fate and promoting disease progression. Targeting these epitranscriptomic changes offers new avenues for cancer biomarkers and precision therapies.
Area of Science:
- The study is situated within molecular biology, focusing on epigenetics and cancer research.
- It specifically investigates the role of RNA modifications in cancer biology.
Background:
- RNA modifications were historically considered static but are now known as dynamic regulators of the epitranscriptome.
- Dysregulation of RNA modification machinery in cancer impacts RNA metabolism, translation, and promotes tumorigenesis, metastasis, therapy resistance, and immune evasion.
Purpose of the Study:
- To review how major RNA modifications (m6A, m5C, pseudouridine, inosine, ac4C) and their regulators contribute to cancer biology.
- To discuss disease-associated changes in ribosomal RNA (rRNA), transfer RNA (tRNA), and non-coding RNAs.
- To explore emerging biomarkers, druggable targets, and combination therapies within the epitranscriptome.
Main Methods:
- A comprehensive review of existing literature on RNA modifications in cancer.
- Comparison of different technologies for mapping RNA modifications, including mass spectrometry, NGS-based methods, and nanopore direct RNA sequencing.
- Highlighting recent technological advancements in single-molecule, multi-modification profiling.
Main Results:
- Aberrant RNA modification patterns drive key cancer processes like alternative splicing, translation, and gene expression.
- Specific modifications and their regulators are implicated in various aspects of cancer development and progression.
- Nanopore direct RNA sequencing shows promise for accelerating discovery in multi-modification profiling.
Conclusions:
- The epitranscriptome is a crucial dimension of cancer biology with potential for diagnostic and prognostic biomarkers.
- Targeting RNA modification machinery presents opportunities for novel, RNA-targeted precision therapies in cancer.
- Integration of epitranscriptomic insights with existing therapies and immunotherapy is a promising strategy.
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